Methionine sulfoxide reductase A (MsrA) restores alpha-crystallin chaperone activity lost upon methionine oxidation.
Methionine sulfoxide reductase A (MsrA) restores alpha-crystallin chaperone activity lost upon methionine oxidation.
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DOI：
10.1016/j.bbagen.2009.08.011
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发表时间：
2009-12
影响因子：
3
通讯作者：
Kantorow, Marc
中科院分区：
文献类型：
--
作者：
Brennan, Lisa A.;Lee, Wanda;Giblin, Frank J.;David, Larry L.;Kantorow, Marc
透镜性白内障与蛋白质氧化和聚集有关。当从透镜缺失时引起白内障的两种蛋白质是甲硫氨酸亚砜还原酶A（MsrA），其修复蛋白质甲硫氨酸亚砜（PMSO）氧化蛋白和α-晶状体蛋白，其是两个亚基（αA和αB）伴侣。在这里，我们测试了PMSO的形成是否会损害α-晶状体蛋白伴侣功能，以及MsrA是否可以修复PMSO-α-晶状体蛋白。将总α-晶状体蛋白氧化为PMSO，并通过CNBr裂解和质谱法进行评价。使用溶菌酶作为靶标通过光散射测量伴侣活性。用MsrA处理PMSO-α-晶状体蛋白，并通过CNBr切割、质谱和伴侣功能的恢复来评估修复。测定相对于野生型小鼠的MsrA敲除小鼠晶状体中的α-stac-PMSO水平。PMSO氧化总α-晶状体蛋白（αA的met 138和αB的met 68）导致α-晶状体蛋白伴侣活性丧失。MsrA处理PMSO-α-晶状体蛋白通过还原PMSO来修复其分子伴侣活性。小鼠MsrA基因缺失导致PMSO-α-晶状体蛋白水平升高。甲硫氨酸氧化损伤α-晶体蛋白伴侣功能，MsrA可修复PMSO-α-晶体蛋白，恢复其伴侣功能。MsrA是维持透镜中α-晶状体蛋白甲硫氨酸还原状态所必需的。α-晶状体蛋白的甲硫氨酸氧化结合MsrA修复的丧失导致α-晶状体蛋白伴侣功能的丧失。由于PMSO水平升高和α-晶状体蛋白功能丧失是白内障的标志，因此这些结果为白内障发展机制以及其他年龄相关疾病的可能机制提供了深入了解。
Lens cataract is associated with protein oxidation and aggregation. Two proteins that cause cataract when deleted from the lens are methionine sulfoxide reductase A (MsrA) that repairs protein methionine sulfoxide (PMSO) oxidized proteins and α-crystallin which is a two subunit (αA and αB) chaperone. Here, we tested whether PMSO formation damages α-crystallin chaperone function and whether MsrA could repair PMSO-α-crystallin. Total α-crystallin was oxidized to PMSO and evaluated by CNBr-cleavage and mass spectrometry. Chaperone activity was measured by light scattering using lysozyme as target. PMSO-α-crystallin was treated with MsrA, and repair was assessed by CNBr cleavage, mass spectrometry and recovery of chaperone function. The levels of α-crystallin-PMSO in the lenses of MsrA-knockout relative to wild-type mice were determined. PMSO oxidation of total α-crystallin (met 138 of αA and met 68 of αB) resulted in loss of α-crystallin chaperone activity. MsrA treatment of PMSO-α-crystallin repaired its chaperone activity through reduction of PMSO. Deletion of MsrA in mice resulted in increased levels of PMSO-α-crystallin. Methionine oxidation damages α-crystallin chaperone function and MsrA can repair PMSO-α-crystallin restoring its chaperone function. MsrA is required for maintaining the reduced state of α-crystallin methionines in the lens. Methionine oxidation of α-crystallin in combination with loss of MsrA repair causes loss of α-crystallin chaperone function. Since increased PMSO levels and loss of α-crystallin function are hallmarks of cataract, these results provide insight into the mechanisms of cataract development and likely those of other age-related diseases.
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DOI：
10.1073/pnas.96.11.6137
发表时间：
1999-05-25
影响因子：
11.1
作者：
Bova, MP;Yaron, O;Horwitz, J
通讯作者：
Horwitz, J
影响因子：
4.8
作者：
Chen, YR;Deterding, LJ;Mason, RP
通讯作者：
Mason, RP
影响因子：
3.5
作者：
Fujii, N;Takeuchi, N;Saito, T
通讯作者：
Saito, T
影响因子：
3.4
作者：
Hanson, SRA;Hasan, A;Smith, JB
通讯作者：
Smith, JB
DOI：
10.1006/bbrc.1995.1391
发表时间：
1995-03-17
影响因子：
3.1
作者：
CHERIAN, M;ABRAHAM, EC
通讯作者：
ABRAHAM, EC